H.pylori, genes and esophageal adenocarcinoma

幽门螺杆菌、基因和食管腺癌

• 批准号: 6915755
• 负责人: GEOFFREY LIU
• 金额: $ 8.75万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6915755
• 关键词: DNA repair; Helicobacter; adenocarcinoma; bacterial disease; cancer risk; clinical research; esophagus neoplasm; gene environment interaction; genetic susceptibility; human subject; inflammation; interleukin 1; myeloperoxidase; neoplasm /cancer epidemiology; questionnaires; single nucleotide polymorphism; superoxide dismutase

DESCRIPTION (provided by applicant): Esophageal adenocarcinoma (EA) has the fastest rising incidence of all cancers in the United States. The overall annual incidence has more than tripled over a twenty year period. These statistics imply an urgent problem that needs addressing, and an environmental component to the etiology and pathogenesis of EA. Although gastroesophageal reflux disease, Barrett's esophagus and obesity are known risk factors for EA, more recently, a protective effect for Helicobacter pylori (HP) has been hypothesized based on the results of several studies. One objective of this research is to confirm earlier results in a large sample of over 250 histologically-confirmed incident EA cases. Through a secondary analysis of data and specimens from two separate molecular epidemiologic studies, the association between Helicobacter pylori and EA risk will be examined via a case-control design, after taking into account important covariates such as gastroesophageal reflux, Barrett's esophagus, and body-mass index. In addition, there may be host factors such as genetic polymorphisms that modify the relationship between HP and EA risk. Genetic polymorphisms involved in three pathways will be evaluated as potential modifiers of this relationship: (a) genes in the inflammatory pathway, such as IL1-beta; (b) genes involved in free radical formation such as MPO and MnSOD; and (c) several candidate DNA repair genes. Both single nucleotide polymorphisms and haplotypes will be evaluated as potential modifiers of the HP-EA risk association. One long-term goal of this small grant project is to generate information that will ultimately lead to a more comprehensive large scale population-based case-control study of EA risks. This application addresses directly priorities set by the NCl, in particular, the recommendations of the Stomach and Esophageal Cancer Progress Report Group (2002), and may have important impact on current medical practices related to the aggressiveness of treating HP infections.

描述（由申请人提供）： 食管腺癌（EA）的发病率最快。在二十年的时间里，年度总数的发展速度超过两倍。这些统计数据意味着需要解决的紧急问题，以及EA的病因和发病机理的环境成分。尽管胃食管反流疾病，巴雷特的食管和肥胖是EA的已知危险因素，但最近已经根据几项研究的结果假设了对幽门螺杆菌（HP）的保护作用。这项研究的一个目的是确认早期的结果，结果是超过250个组织学确认的EA病例的大量样本。通过对两个单独的分子流行病学研究的数据和标本进行次要分析，将在考虑到重要协变量（例如胃食管反流器）之后，通过病例对照设计来检查幽门螺杆菌和EA风险之间的关联。质量指数。此外，可能还有宿主因素，例如遗传多态性，可以改变HP与EA风险之间的关系。涉及三种途径的遗传多态性将被评估为这种关系的潜在修饰符：（a）炎症途径中的基因，例如IL1-beta； （b）参与自由基形成的基因，例如MPO和MNSOD； （c）几个候选DNA修复基因。单核苷酸多态性和单倍型都将被评估为HP-EA风险关联的潜在修饰符。这个小型赠款项目的一个长期目标是生成信息，这些信息最终将导致更全面的大规模基于人口的EA风险研究。该申请直接解决了NCL设定的优先级，特别是胃和食管癌进度报告小组（2002）的建议，可能对与治疗HP感染的侵略性有关的当前医学实践产生重要影响。